5-113043587-A-C

Variant names:

• chr5-113043587-A-C
• NM_001085377.2:c.2699T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001085377.2(MCC):​c.2699T>G​(p.Leu900Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCC NM_001085377.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

Genes affected

MCC (HGNC:6935): (MCC regulator of WNT signaling pathway) This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCC	NM_001085377.2	c.2699T>G	p.Leu900Arg	missense_variant	Exon 17 of 19	ENST00000408903.7	NP_001078846.2
MCC	NM_002387.3	c.2129T>G	p.Leu710Arg	missense_variant	Exon 15 of 17		NP_002378.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCC	ENST00000408903.7	c.2699T>G	p.Leu900Arg	missense_variant	Exon 17 of 19	2	NM_001085377.2	ENSP00000386227.3
MCC	ENST00000302475.9	c.2129T>G	p.Leu710Arg	missense_variant	Exon 15 of 17	1		ENSP00000305617.4
MCC	ENST00000515367.6	c.1940T>G	p.Leu647Arg	missense_variant	Exon 15 of 17	5		ENSP00000421615.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2699T>G (p.L900R) alteration is located in exon 17 (coding exon 17) of the MCC gene. This alteration results from a T to G substitution at nucleotide position 2699, causing the leucine (L) at amino acid position 900 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;.;.
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.19	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.039	D;D;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.77	P;.;D
Vest4		0.61
MutPred		0.25		Loss of stability (P = 0.0134);.;.;
MVP		0.52
MPC		0.18
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.32
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112379284;